中国临床药学杂志

目的建立测定大鼠血中胆碱酯酶抑制剂XQ528及其代谢物美普他酚浓度的高效液相-质谱联用法(LC-MS/MS)。方法血浆样品采用乙腈沉淀蛋白后进样测定,以尼泊金乙酯为内标。色谱柱:ZORBAX Eclipse XDB C18(50 mm×2.1mm,5μm),流动相:水(0.1%甲酸,A)-乙腈(0.1%甲酸,B),梯度洗脱,流速0.4 m L·min-1,柱温30℃,进样量20μL,总分析时间为7 min。质谱采用电喷雾离子源,以多反应离子监测模式进行定量分析。结果 XQ528及其代谢物美普他酚的线性范围分别为0.05~50μg·L-1和0.05~25μg·L-1;批内RSD分别为3.1%和9.4%,批间RSD分别为7.4%和8.6%;提取回收率分别为102.1%~103.3%和104.2%~110.0%;基质效应均在85%~115%内。结论本方法灵敏度高、准确、快速,适于大鼠血浆中XQ528及其代谢物美普他酚浓度的测定和药动学研究。

AIM To develop an LC-MS/MS method for determination of cholinesterase inhibitor XQ528 and its metabolite meptazinol in rat plasma. METHODS The analytes and the internal standard( IS,ethylparaben) were extracted from 50 μL aliquots of rat plasma by acetonitrile precipitation. Chromatographic separation was achieved by gradient elution on a ZORBAX Eclipse XDB C18column( 50 mm × 2. 1 mm,5 μm) in a run time of 7 min with the mobile phase consisted of water( 0. 1% formic acid,A) and acetonitrile( 0. 1% formic acid,B),which was pumped at a flow rate of 0. 4 m L·min- 1. The column temperature was set at 30℃ and the injection volume was 20 μL. Detection of analytes and IS was done by tandem mass spectrometry,operated in positive ion and multiple reaction monitoring( MRM)mode. RESULTS The liner range of XQ528 and meptazinol in rats plasma were 0. 05- 50 μg·L- 1and 0. 05- 25 μg·L- 1,respectively. The intra-batch RSD were less than 3.1% and 9.4% respectively,and the inter-batch RSD were less than 7. 4% and 8. 6% respectively. The extraction recoveries were 102. 1%- 103. 3% and 104. 2%- 110. 0%,respectively. The matrix effects were all within 85%- 115%. CONCLUSION The method is sensitive,accurate and fast,and suitable for the pharmacokinetic study of XQ528 formulation.